This study investigated the effect of age and that of the post-ovariectomy (OVX) time interval on the antidepressant (AD)-like effects of estradiol (E2) and selective serotonin reuptake inhibitors (SSRIs) in middle-aged (10 month) OVX rats (10m-OVX). Acute or chronic effects of these treatments in 10m-OVX were compared with those (1) in young adult (4-month) OVX rats (4m-OVX) or with older (14-month) OVX rats (14m-OVX), at a short time: 2 weeks post-OVX (+2w) and (2) in 10m-OVX rats after a longer times: 4 or 8 months post-OVX (+4m or +8m). Using in vivo chronoamperometry in the CA3 region of the hippocampus, E2 at 20 pmol, a dose shown previously to inhibit the serotonin transporter (SERT) in 4m-OVX, had no effect in 10m-OVX+2w. A higher dose of E2 (40 pmol) increased T80 value, a measure of serotonin or 5-hydroxytryptamine (5-HT) clearance, and also blocked the ability of fluvoxamine to increase T80. By contrast, estradiol had no effects on SERT function in 10m-OVX+4m, even at a higher dose than 40 pmol. Fluvoxamine slowed 5-HT clearance in 10m-OVX at +2w, +4m and +8m post-OVX as it did in the 4m-OVX. Using the forced swim test, 2 weeks treatment with E2 (5 μg/day), a dose shown previously to induce AD-like effects in 4m-OVX, had no effect in 10m-OVX+2w. However, a higher dose (10 μg/day) of E2 induced an AD-like effect as demonstrated by significantly increased swimming behavior and decreased immobility. This effect was not seen in 10m-OVX+4m. By contrast, significant AD-like effects were obtained in 14m-OVX+2w, thereby demonstrating that the lack of an AD effect of E2 is due to the 4-month hormone withdrawal and not to an age effect. After 2 weeks treatment with the SSRI sertraline, similar AD-like effects were obtained in 10m-OVX tested at +2w, +4m or +8m post-OVX as those found in 4m-OVX. Thus, the potency of estradiol to produce effects consistent with inhibition of the SERT was not only decreased in older rats but its effects were markedly diminished the longer hormonal depletion occurred. By contrast, the ability of SSRIs to inhibit the SERT was not affected either by age or the length of hormonal depletion.
Pharmacology, Toxicology and Pharmaceutical Science
6
17%
Medicine and Dentistry
2
6%
Biochemistry, Genetics and Molecular Biology
1
3%
Agricultural and Biological Sciences
1
3%
Other
3
9%
Unknown
14
40%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 December 2016.
All research outputs
#18,025,678
of 26,450,025 outputs
Outputs from Frontiers in Aging Neuroscience
#4,321
of 5,710 outputs
Outputs of similar age
#273,288
of 428,384 outputs
Outputs of similar age from Frontiers in Aging Neuroscience
#72
of 93 outputs
Altmetric has tracked 26,450,025 research outputs across all sources so far. This one is in the 31st percentile – i.e., 31% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,710 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.6. This one is in the 23rd percentile – i.e., 23% of its peers scored the same or lower than it.
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We're also able to compare this research output to 93 others from the same source and published within six weeks on either side of this one. This one is in the 20th percentile – i.e., 20% of its contemporaries scored the same or lower than it.
